Abstract The Acute Respiratory Distress Syndrome (ARDS) is a major cause of mortality and morbidity in critically ill patients, with an estimated mortality rate of 30-40%. Despite the widespread recognition of low tidal volume ventilation (LTVV) as the only known therapy to reduce mortality in ARDS (in a randomized clinical trial, LTVV reduced mortality from 40% to 31%, a remarkable absolute reduction for a single treatment strategy), compliance with LTVV remains low. Representative of other studies to date, preliminary data from our research group at UCSF indicates that less than 25% of all ARDS patients achieve LTVV as defined as a tidal volume of ? 6.5 cc/kg of predicted body weight. A better understanding of the patient, provider, and ICU organizational characteristics that increase the risk of failure to receive LTVV is critical if we are to improve outcomes for patients with ARDS. Furthermore, it is unknown whether the mortality benefit derived from LTVV is time- dependent, either with regards to the time needed to achieve LTVV or proportion of time receiving this ventilation strategy. Other supportive interventions, such as treatment with appropriate antibiotics, are clearly time-dependent (e.g., time to appropriate antibiotic therapy and duration of appropriate treatment are both associated with improved outcomes), so it is reasonable to hypothesize that similar principles apply to low tidal volume ventilation. The studies proposed in this application will test the hypothesis that specific patient and physician characteristics place patients at risk for failure to receive LTVV (Aim 1), in particular lower rates of recognition of ARDS in patients with mild-moderate disease severity (Hypothesis 1A), and that tidal volumes are more likely to be off-target during the evening shift as compared with day shift (Hypothesis 1B).Furthermore, we will test whether the to achieve LTVV from the onset of ARDS, and the proportion of time during which LTVV was administered as a function of total time receiving mechanical ventilation are associated with patient outcomes (Aim 2). Finally, we hypothesize that an institutional approach incorporating low-tidal volume ventilation as a recommended default and initial ventilator strategy will improve compliance with LTVV, decrease time needed to achieve a LTVV, increase the proportion of time of receipt of LTVV, and result in overall lower tidal volumes achieved in cc/kg of predicted body weight (Aim 3). This project will have an important and favorable impact on clinical outcomes in ARDS patients by elucidating patient and process characteristics that place patients at risk for receipt of off-target tidal volumes, further defining the association between timely and sustained receipt of LTVV on mortality and ARDS outcomes, and testing the efficacy of a rigorous quality improvement measure to improve adherence to LTVV. This project will also pave the way for a K23 project to study the impact and efficacy of quality improvement measures geared towards increasing adherence to LTVV and will also facilitate my long-term career goals to improve the care of critically ill patients through studying the science of implementation and the systematic application of evidence-based practices.